tbuckley/cabot-search huggingface dataset:
circPSD3 is a promising inhibitor of uPA system to inhibit vascular invasion and metastasis in hepatocellular carcinoma
Authors: Liangliang Xu, Peng Wang, Li Li, Lian Li, Yang Huang, Yanfang Zhang, Xiaobo Zheng, Pengsheng Yi, Ming Zhang, Mingqing Xu
Journal: Molecular Cancer (2023)

Vascular invasion is a major route for intrahepatic and distant metastasis in hepatocellular carcinoma (HCC) and is a strong negative prognostic factor. Circular RNAs (circRNAs) play important roles in tumorigenesis and metastasis. However, the regulatory functions and underlying mechanisms of circRNAs in the development of vascular invasion in HCC are largely unknown.
A Step Forward in Solving Amyloidosis
Authors: Giampaolo Merlini
Journal: New England Journal of Medicine (2023)

Systemic amyloidoses are characterized by protein misfolding with tissue deposition of insoluble beta-sheet fibrils.1 The two most common forms of amyloid cardiomyopathy are caused by the aggregation of transthyretin (causing transthyretin amyloidosis, also called ATTR amyloidosis) and of monoclonal immunoglobulin light chains (causing immunoglobulin light-chain [AL] amyloidosis). Most circulating transthyretin, a homotetrameric thyroxine and vitamin A transport protein, is produced in the liver; the remainder is produced by the choroid plexus and retina. Germline pathogenic variants of the TTR gene result in unstable mutant transthyretin and cause autosomal dominant hereditary, also known as variant, ATTR amyloidosis. In aging adults who . . .
Medication Abortion Safety and Effectiveness With Misoprostol Alone
Authors: Ruvani Jayaweera, Ijeoma Egwuatu, Sybil Nmezi, Ika Ayu Kristianingrum, Ruth Zurbriggen, Belén Grosso, Chiara Bercu, Caitlin Gerdts, Heidi Moseson
Journal: JAMA Network Open (2023)

Importance Misoprostol-alone regimens for abortion may be more effective than previously thought. Objective To estimate the effectiveness of medication abortion with misoprostol alone among individuals self-managing their abortion. Design, Setting, and Participants For this prospective observational cohort study of callers to safe abortion hotlines and accompaniment groups in Argentina, Nigeria, and Southeast Asia, participants were recruited between July 31, 2019, and October 1, 2020, prior to starting their medication abortion. Eligible participants were 13 years or older, had no contraindications to medication abortion, and were not currently bleeding. Participants completed a baseline and 2 follow-up surveys. The analysis was restricted to participants who reported using misoprostol alone and was performed between January 6, 2022 and September 8, 2023. Exposure Self-managed medication abortion using misoprostol alone. Main Outcomes and Measures The primary outcome was effectiveness, defined as participant self-report of complete abortion without procedural intervention, measured at 1 week and 3 weeks after taking misoprostol. Secondary outcomes included method safety, measured by self-report of experiencing warning signs (eg, heavy bleeding, pain, fever, discharge) indicative of a potential complication and by medical treatment (eg, blood transfusion, intravenous fluids, overnight hospital stay) indicative of a potential adverse event. Additional outcomes included length of bleeding and cramping, time to expulsion, and experience of adverse effects. Results Among 1352 enrolled participants, 637 used misoprostol-alone regimens for abortion and were included in the analysis (591 [92.8%] from Nigeria, 45 [7.1%] from Southeast Asia, and 1 [0.2%] from Argentina; 384 [60.2%] aged 20-29 years; 317 [49.8%] with pregnancy durations &amp;amp;lt;7 weeks and 205 [32.2%] with pregnancy durations between 7 and &amp;amp;lt;9 weeks). At last follow-up after taking medication (median, 22 days; IQR, 21-26 days), 625 participants (98.1%; 95% CI, 96.7%-98.9%) had a complete abortion without procedural intervention. Potential adverse events were reported by 6 participants (0.9%; 95% CI, 0.4%-2.1%). Most participants experienced bleeding for less than 1 week (median, 4 days; IQR, 3-6 days) and expelled their pregnancy within 24 hours of starting the abortion process (median, 12 hours; IQR, 9-15 hours). Common side effects included nausea (335 participants [52.6%]), fever (232 [36.4%]), and diarrhea (181 [28.4%]). Conclusions and Relevance The findings suggest that misoprostol alone is a highly effective method of pregnancy termination. Future research should explore strategies to maximize the effectiveness of misoprostol alone in clinical and nonclinical settings.
Flecainide Is Associated With a Lower Incidence of Arrhythmic Events in a Large Cohort of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Auke T. Bergeman, Krystien V.V. Lieve, Dania Kallas, J. Martijn Bos, Ferran Rosés i Noguer, Isabelle Denjoy, Esther Zorio, Janneke A.E. Kammeraad, Puck J. Peltenburg, Katie Tobert, Takeshi Aiba, Joseph Atallah, Fabrizio Drago, Anjan S. Batra, Ramon Brugada, Martin Borggrefe, Sally-Ann B. Clur, Moniek G.P.J. Cox, Andrew Davis, Santokh Dhillon, Susan P. Etheridge, Peter Fischbach, Sonia Franciosi, Kristina Haugaa, Minoru Horie, Christopher Johnsrude, Austin M. Kane, Ulrich Krause, Sit-Yee Kwok, Martin J. LaPage, Seiko Ohno, Vincent Probst, Jason D. Roberts, Tomas Robyns, Frederic Sacher, Christopher Semsarian, Jonathan R. Skinner, Heikki Swan, Terezia Tavacova, Svjetlana Tisma-Dupanovic, Jacob Tfelt-Hansen, Sing-Chien Yap, Prince J. Kannankeril, Antoine Leenhardt, Janice Till, Shubhayan Sanatani, Michael W.T. Tanck, Michael J. Ackerman, Arthur A.M. Wilde, Christian van der Werf
Journal: Circulation (2023)

In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia.
Reciprocal stabilization of coagulation factor XIII-A and -B subunits is a determinant of plasma FXIII concentration
Authors: James R. Byrnes, Taek Lee, Sherif Sharaby, Robert A. Campbell, Dre’Von A. Dobson, Lori A. Holle, Michelle Luo, Kadri Kangro, Jonathon W. Homeister, Maria M. Aleman, James P. Luyendyk, Bryce A. Kerlin, Julie B. Dumond, Alisa S. Wolberg
Journal: Blood (2023)
Phase 3 Trial of Nemolizumab in Patients with Prurigo Nodularis
Authors: Shawn G. Kwatra, Gil Yosipovitch, Franz J. Legat, Adam Reich, Carle Paul, Dagmar Simon, Luigi Naldi, Charles Lynde, Marjolein S. De Bruin-Weller, Walter K. Nahm, Maxwell Sauder, Rola Gharib, Sebastien Barbarot, Jacek C. Szepietowski, Curdin Conrad, Alan Fleischer, Vivian T. Laquer, Laurent Misery, Esther Serra-Baldrich, Hilde Lapeere, Faiz Ahmad, Zarif K. Jabbar Lopez, Christophe Piketty, Sonja Ständer
Journal: New England Journal of Medicine (2023)

Prurigo nodularis is a chronic, debilitating, and severely pruritic neuroimmunologic skin disease. Nemolizumab, an interleukin-31 receptor alpha antagonist, down-regulates key pathways in the pathogenesis of prurigo nodularis. Download a PDF of the Research Summary. In this phase 3, double-blind, multicenter, randomized trial, we assigned adults with moderate-to-severe prurigo nodularis to receive an initial 60-mg dose of nemolizumab followed by subcutaneous injections of 30 mg or 60 mg (depending on baseline weight) every 4 weeks for 16 weeks or matching placebo. The primary end points were an itch response (a reduction of ≥4 points on the Peak Pruritus Numerical Rating Scale [PP-NRS; scores range from 0 to 10, with higher scores indicating more severe itch]) and an Investigator's Global Assessment (IGA) response (a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4] and a reduction from baseline to week 16 of ≥2 points). There were five key secondary end points. A total of 274 patients underwent randomization; 183 were assigned to the nemolizumab group, and 91 to the placebo group. Treatment efficacy was shown with respect to both primary end points at week 16; a greater percentage of patients in the nemolizumab group than in the placebo group had an itch response (56.3% vs. 20.9%; strata-adjusted difference, 37.4 percentage points; 95% confidence interval [CI], 26.3 to 48.5), and a greater percentage in the nemolizumab group had an IGA response (37.7% vs. 11.0%; strata-adjusted difference, 28.5 percentage points; 95% CI, 18.8 to 38.2) (P<0.001 for both comparisons). Benefits were observed for the five key secondary end points: itch response at week 4 (41.0% vs. 7.7%), PP-NRS score of less than 2 at week 4 (19.7% vs. 2.2%) and week 16 (35.0% vs. 7.7%), and an improvement of 4 or more points on the sleep disturbance numerical rating scale (range, 0 [no sleep loss] to 10 [unable to sleep at all]) at week 4 (37.2% vs. 9.9%) and week 16 (51.9% vs. 20.9%) (P<0.001 for all comparisons). The most common individual adverse events were headache (6.6% vs. 4.4%) and atopic dermatitis (5.5% vs. 0%). Nemolizumab monotherapy significantly reduced the signs and symptoms of prurigo nodularis. (Funded by Galderma; ClinicalTrials.gov number, NCT04501679; EudraCT number, 2019-004789-17.) QUICK TAKE VIDEO SUMMARYNemolizumab for Prurigo Nodularis 02:03
Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma: Externally Controlled, Propensity Score–Matched Survival Outcome Comparisons
Authors: Javier Oesterheld, William Ferguson, Jacqueline M. Kraveka, Genevieve Bergendahl, Thomas Clinch, Elizabeth Lorenzi, Don Berry, Randal K. Wada, Michael S. Isakoff, Don E. Eslin, Valerie I. Brown, William Roberts, Peter Zage, Virginia L. Harrod, Deanna S. Mitchell, Derek Hanson, Giselle L. Saulnier Sholler
Journal: Journal of Clinical Oncology (2023)

Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion of immunotherapy was investigated previously in a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free survival (EFS) and overall survival (OS) compared with historical rates in a phase III trial (Children Oncology Group ANBL0032; ClinicalTrials.gov identifier: NCT00026312). Using patient-level data from ANBL0032 as an external control, we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance.NMTRC003B (2012-2016) enrolled patients with HRNB (N = 141) after standard up-front or refractory/relapse treatment who received up to 2 years of continuous treatment with oral DFMO (750 ± 250 mg/m2 twice a day). ANBL0032 (2001-2015) enrolled patients with HRNB postconsolidation, 1,328 of whom were assigned to dinutuximab (ch.14.18) treatment. Selection rules identified 92 NMTRC003B patients who participated in (n = 87) or received up-front treatment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who could have been eligible for NMTRC003B after immunotherapy, but did not enroll (the NO-DFMO/control group). The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients. Kaplan-Meier and Cox regression compared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on 11 baseline demographic and disease characteristics with exact matching on MYCN, and additional sensitivity analyses.DFMO after completion of immunotherapy was associated with improved EFS (hazard ratio [HR], 0.50 [95% CI, 0.29 to 0.84]; P = .008) and OS (HR, 0.38 [95% CI, 0.19 to 0.76]; P = .007). The results were confirmed with propensity score-matched cohorts and sensitivity analyses.The externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.
Prodrug-based strategy with a two-in-one liposome for Cerenkov-induced photodynamic therapy and chemotherapy
Authors: Huihui Liu, Qing Wang, Jingru Guo, Kai Feng, Yiling Ruan, Zhihao Zhang, Xin Ji, Jigang Wang, Tao Zhang, Xiaolian Sun
Journal: Journal of Controlled Release (2023)
Granzyme B production by Th2 helper and <scp>NK</scp> cells improves the <scp>LTT</scp> test in patients with non‐immediate drug hypersensitivity reactions
Authors: Lars H. Blom, Lasse B. Schmidt, Claus R. Johnsen, Jesper Elberling, Lars K. Poulsen, Lene H. Garvey
Journal: Allergy (2023)
SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials
Authors: Benedetta Conte, Luca Boni, Giancarlo Bisagni, Antonio Durando, Giovanni Sanna, Stefania Gori, Ornella Garrone, Stefano Tamberi, Sabino De Placido, Francesco Schettini, Antonio Pazzola, Riccardo Ponzone, Filippo Montemurro, Gianluigi Lunardi, Rosario Notaro, Maria De Angioletti, Anna Turletti, Mauro Mansutti, Fabio Puglisi, Antonio Frassoldati, Mauro Porpiglia, Alessandra Fabi, Daniele Generali, Giovanni Scognamiglio, Maura Rossi, Fara Brasó-Maristany, Aleix Prat, Barbara Cardinali, Patrizia Piccioli, Martina Serra, Sonia Lastraioli, Claudia Bighin, Francesca Poggio, Matteo Lambertini, Lucia Del Mastro
Journal: Clinical Cancer Research (2023)

Abstract Purpose: In estrogen receptor–positive (ER+) breast cancer, single-nucleotide polymorphisms (SNP) in the aromatase gene might affect aromatase inhibitors (AI) metabolism and efficacy. Here, we assessed the impact of SNP on prognosis and toxicity of patients receiving adjuvant letrozole. Experimental Design: We enrolled 886 postmenopausal patients in the study. They were treated with letrozole for 2 to 5 years after taking tamoxifen for 2 to 6 years, continuing until they completed 5 to 10 years of therapy. Germline DNA was genotyped for SNP rs4646, rs10046, rs749292, and rs727479. Log-rank test and Cox model were used for disease-free survival (DFS) and overall survival (OS). Cumulative incidence (CI) of breast cancer metastasis was assessed through competing risk analysis, with contralateral breast cancer, second malignancies and non-breast cancer death as competing events. CI of skeletal and cardiovascular events were assessed using DFS events as competing events. Subdistribution HR (sHR) with 95% confidence intervals were calculated through Fine-Gray method. Results: No SNP was associated with DFS. Variants rs10046 [sHR 2.03, (1.04–2.94)], rs749292 [sHR 2.11, (1.12–3.94)], and rs727479 [sHR 2.62, (1.17–5.83)] were associated with breast cancer metastasis. Three groups were identified on the basis of the number of these variants (0, 1, &amp;gt;1). Variant-based groups were associated with breast cancer metastasis (10-year CI 2.5%, 7.6%, 10.7%, P = 0.035) and OS (10-year estimates 96.5%, 93.0%, 89.6%, P = 0.030). Co-occurrence of rs10046 and rs749292 was negatively associated with 10-year CI of skeletal events (3.2% vs. 10%, P = 0.033). A similar association emerged between rs727479 and cardiovascular events (0.3% vs. 2.1%, P = 0.026). Conclusions: SNP of aromatase gene predict risk of metastasis and AI-related toxicity in ER+ early breast cancer, opening an opportunity for better treatment individualization.
Resolvin <scp>D2</scp> regulates type 2 inflammatory responses and promotes resolution of mouse allergic inflammation
Authors: Hong Yong Peh, Thayse R. Brüggemann, Melody G. Duvall, Robert Nshimiyimana, Julie Nijmeh, Maria A. Cinelli, Elliot Israel, Charles N. Serhan, Bruce D. Levy
Journal: Allergy (2023)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes
Authors: Vasiliki Pavlou, Sofia Cienfuegos, Shuhao Lin, Mark Ezpeleta, Kathleen Ready, Sarah Corapi, Jackie Wu, Jason Lopez, Kelsey Gabel, Lisa Tussing-Humphreys, Vanessa M. Oddo, Shaina J. Alexandria, Julienne Sanchez, Terry Unterman, Lisa S. Chow, Alaina P. Vidmar, Krista A. Varady
Journal: JAMA Network Open (2023)

Importance Time-restricted eating (TRE) has become increasingly popular, yet longer-term randomized clinical trials have not evaluated its efficacy and safety in patients with type 2 diabetes (T2D). Objective To determine whether TRE is more effective for weight reduction and glycemic control than daily calorie restriction (CR) or a control condition in adults with T2D. Design, Setting, and Participants This 6-month, parallel-group, randomized clinical trial was performed between January 25, 2022, and April 1, 2023, at the University of Illinois Chicago. Participants were aged 18 to 80 years with obesity and T2D. Data analysis was based on intention to treat. Interventions Participants were randomized to 1 of 3 groups: 8-hour TRE (eating 12 to 8 pm only, without calorie counting), CR (25% energy restriction daily), or control. Main Outcomes and Measures The primary outcome measure was change in body weight by month 6. Secondary outcomes included changes in hemoglobin A 1c (HbA 1c ) levels and metabolic risk factors. Results Seventy-five participants were enrolled with a mean (SD) age of 55 (12) years. The mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39 (7) and the mean (SD) HbA 1c level was 8.1% (1.6%). A total of 53 participants (71%) were women. One participant (1%) was Asian, 30 (40%) were Hispanic White, 40 (53%) were non-Hispanic Black, and 4 (5%) were non-Hispanic White. Participants in the TRE group were adherent with their eating window on a mean (SD) of 6.1 (0.8) days per week, and 17 (68%) in the CR group were adherent with their prescribed calorie goals over 6 months. The mean (SD) reduction in energy intake was −313 (509) kcal/d for TRE, −197 (426) kcal/d for CR, and −16 (439) kcal/d for controls. By month 6, body weight decreased significantly in the TRE group (−3.56% [95% CI, −5.92% to −1.20%]; P = .004) but not the CR group (−1.78% [95% CI, −3.67% to 0.11%]; P = .06), relative to controls. Levels of HbA 1c decreased in the TRE (−0.91% [95% CI, −1.61% to −0.20%]) and CR (−0.94% [95% CI, −1.59% to −0.30%]) groups, relative to controls, with no differences between the TRE and CR groups. Time in euglycemic range, medication effect score, blood pressure, and plasma lipid levels did not differ among groups. No serious adverse events were reported. Conclusions and relevance This randomized clinical trial found that a TRE diet strategy without calorie counting was effective for weight loss and lowering of HbA 1c levels compared with daily calorie counting in a sample of adults with T2D. These findings will need to be confirmed by larger RCTs with longer follow-up. Trial Registration ClinicalTrials.gov Identifier: NCT05225337
IL-20 controls resolution of experimental colitis by regulating epithelial IFN/STAT2 signalling
Authors: Mircea Teodor Chiriac, Zsuzsanna Hracsko, Claudia Günther, Miguel Gonzalez-Acera, Raja Atreya, Iris Stolzer, Leonie Wittner, Anja Dressel, Laura Schickedanz, Reyes Gamez-Belmonte, Lena Erkert, Gheorghe Hundorfean, Sebastian Zundler, Timo Rath, Stefania Vetrano, Silvio Danese, Gregor Sturm, Zlatko Trajanoski, Anja A Kühl, Britta Siegmund, Arndt Hartmann, Stefan Wirtz, Jürgen Siebler, Susetta Finotto, Christoph Becker, Markus F Neurath
Journal: Gut (2023)

Objective We sought to investigate the role of interleukin (IL)-20 in IBD and experimental colitis. Design Experimental colitis was induced in mice deficient in components of the IL-20 and signal transducer and activator of transcription (STAT)2 signalling pathways. In vivo imaging, high-resolution mini-endoscopy and histology were used to assess intestinal inflammation. We further used RNA-sequencing (RNA-Seq), RNAScope and Gene Ontology analysis, western blot analysis and co-immunoprecipitation, confocal microscopy and intestinal epithelial cell (IEC)-derived three-dimensional organoids to investigate the underlying molecular mechanisms. Results were validated using samples from patients with IBD and non-IBD control subjects by a combination of RNA-Seq, organoids and immunostainings. Results In IBD, IL20 levels were induced during remission and were significantly higher in antitumour necrosis factor responders versus non-responders. IL-20RA and IL-20RB were present on IECs from patients with IBD and IL-20-induced STAT3 and suppressed interferon (IFN)-STAT2 signalling in these cells. In IBD, experimental dextran sulfate sodium (DSS)-induced colitis and mucosal healing, IECs were the main producers of IL-20. Compared with wildtype controls, Il20 −/− , Il20ra −/− and Il20rb −/− mice were more susceptible to experimental DSS-induced colitis. IL-20 deficiency was associated with increased IFN/STAT2 activity in mice and IFN/STAT2-induced necroptotic cell death in IEC-derived organoids could be markedly blocked by IL-20. Moreover, newly generated Stat2 ΔIEC mice, lacking STAT2 in IECs, were less susceptible to experimental colitis compared with wildtype controls and the administration of IL-20 suppressed colitis activity in wildtype animals. Conclusion IL-20 controls colitis and mucosal healing by interfering with the IFN/STAT2 death signalling pathway in IECs. These results indicate new directions for suppressing gut inflammation by modulating IL-20-controlled STAT2 signals.
Prognosis Individualized: Survival predictions for WHO grade II and III gliomas with a machine learning-based web application
Authors: Mert Karabacak, Pemla Jagtiani, Alejandro Carrasquilla, Isabelle M. Germano, Konstantinos Margetis
Journal: npj Digital Medicine (2023)

WHO grade II and III gliomas demonstrate diverse biological behaviors resulting in variable survival outcomes. In the context of glioma prognosis, machine learning (ML) approaches could facilitate the navigation through the maze of factors influencing survival, aiding clinicians in generating more precise and personalized survival predictions. Here we report the utilization of ML models in predicting survival at 12, 24, 36, and 60 months following grade II and III glioma diagnosis. From the National Cancer Database, we analyze 10,001 WHO grade II and 11,456 grade III cranial gliomas. Using the area under the receiver operating characteristic (AUROC) values, we deploy the top-performing models in a web application for individualized predictions. SHapley Additive exPlanations (SHAP) enhance the interpretability of the models. Top-performing predictive models are the ones built with LightGBM and Random Forest algorithms. For grade II gliomas, the models yield AUROC values ranging from 0.813 to 0.896 for predicting mortality across different timeframes, and for grade III gliomas, the models yield AUROCs ranging from 0.855 to 0.878. ML models provide individualized survival forecasts for grade II and III glioma patients across multiple clinically relevant time points. The user-friendly web application represents a pioneering digital tool to potentially integrate predictive analytics into neuro-oncology clinical practice, to empower prognostication and personalize clinical decision-making.